17-50346186-C-T

Variant names:

• chr17-50346186-C-T
• rs1254511984
• NM_022167.4:c.46C>T

Variant summary

Our verdict is Likely benign. The variant received -3 ACMG points: 2P and 5B. PM2 BP4_Moderate BP6_Moderate BP7

The NM_022167.4(XYLT2):​c.46C>T​(p.Leu16Leu) variant causes a synonymous change involving the alteration of a non-conserved nucleotide. The variant allele was found at a frequency of 0.00000232 in 1,291,506 control chromosomes in the GnomAD database, with no homozygous occurrence. In-silico tool predicts a benign outcome for this variant. Variant has been reported in ClinVar as Likely benign (★).

• Frequency:
  • Genomes: 𝑓 0.0000068 (0 hom., cov: 32)
  • Exomes 𝑓: 0.0000017 (0 hom.)
• Consequence: XYLT2 NM_022167.4 synonymous
• Clinical Significance: Likely benign criteria provided, single submitter B:1
• Conservation: PhyloP100: 2.23
• Publications: 0 publications found

Genes affected

XYLT2 (HGNC:15517): (xylosyltransferase 2) The protein encoded by this gene is an isoform of xylosyltransferase, which belongs to a family of glycosyltransferases. This enzyme transfers xylose from UDP-xylose to specific serine residues of the core protein and initiates the biosynthesis of glycosaminoglycan chains in proteoglycans including chondroitin sulfate, heparan sulfate, heparin and dermatan sulfate. The enzyme activity, which is increased in scleroderma patients, is a diagnostic marker for the determination of sclerotic activity in systemic sclerosis. Alternatively spliced transcript variants have been found for this gene. [provided by RefSeq, Dec 2013]

XYLT2 Gene-Disease associations (from GenCC):

• spondylo-ocular syndrome

  Inheritance: AR Classification: STRONG, SUPPORTIVE Submitted by: Labcorp Genetics (formerly Invitae), Orphanet, G2P

ACMG classification

Our verdict: Likely_benign. The variant received -3 ACMG points.

• PM2: Very rare variant in population databases, with high coverage
• BP4: Computational evidence support a benign effect (BayesDel_noAF=-0.39).
• BP6: Variant 17-50346186-C-T is Benign according to our data. Variant chr17-50346186-C-T is described in ClinVar as Likely_benign. ClinVar VariationId is 2985875.Status of the report is criteria_provided_single_submitter, 1 stars.
• BP7: Synonymous conserved (PhyloP=2.22 with no splicing effect.

Variant Effect in Transcripts

ACMG analysis was done for transcript: NM_022167.4. You can select a different transcript below to see updated ACMG assignments.

RefSeq Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLT2	NM_022167.4	MANE Select	c.46C>T	p.Leu16Leu	synonymous	Exon 1 of 11	NP_071450.2	Q9H1B5-1
	XYLT2	NR_110010.2		n.61C>T		non_coding_transcript_exon	Exon 1 of 10

Ensembl Transcripts

Sel.	Gene	Transcript	Tags	HGVSc	HGVSp	Effect	Exon Rank	Protein	UniProt
	XYLT2	ENST00000017003.7	TSL:1 MANE Select	c.46C>T	p.Leu16Leu	synonymous	Exon 1 of 11	ENSP00000017003.2	Q9H1B5-1
	XYLT2	ENST00000376550.7	TSL:1	n.46C>T		non_coding_transcript_exon	Exon 1 of 10	ENSP00000365733.3	A0A0C4DFW8
	XYLT2	ENST00000854775.1		c.46C>T	p.Leu16Leu	synonymous	Exon 1 of 11	ENSP00000524834.1

Frequencies

GnomAD3 genomes AF: 0.00000675 AC: 1 AN: 148048 Hom.: 0 Cov.: 32

Gnomad AFR AF: 0.0000243

Gnomad AMI AF: 0.00

Gnomad AMR AF: 0.00

Gnomad ASJ AF: 0.00

Gnomad EAS AF: 0.00

Gnomad SAS AF: 0.00

Gnomad FIN AF: 0.00

Gnomad MID AF: 0.00

Gnomad NFE AF: 0.00

Gnomad OTH AF: 0.00

GnomAD4 exome AF: 0.00000175 AC: 2 AN: 1143458 Hom.: 0 Cov.: 30 AF XY: 0.00000177 AC XY: 1 AN XY: 563586

African (AFR) AF: 0.00 AC: 0 AN: 21998

American (AMR) AF: 0.0000491 AC: 1 AN: 20374

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 16676

East Asian (EAS) AF: 0.00 AC: 0 AN: 17282

South Asian (SAS) AF: 0.00 AC: 0 AN: 64380

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 30660

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 3162

European-Non Finnish (NFE) AF: 0.00000108 AC: 1 AN: 927138

Other (OTH) AF: 0.00 AC: 0 AN: 41788

GnomAD4 genome AF: 0.00000675 AC: 1 AN: 148048 Hom.: 0 Cov.: 32 AF XY: 0.00 AC XY: 0 AN XY: 72090

African (AFR) AF: 0.0000243 AC: 1 AN: 41090

American (AMR) AF: 0.00 AC: 0 AN: 14894

Ashkenazi Jewish (ASJ) AF: 0.00 AC: 0 AN: 3404

East Asian (EAS) AF: 0.00 AC: 0 AN: 5160

South Asian (SAS) AF: 0.00 AC: 0 AN: 4832

European-Finnish (FIN) AF: 0.00 AC: 0 AN: 8986

Middle Eastern (MID) AF: 0.00 AC: 0 AN: 312

European-Non Finnish (NFE) AF: 0.00 AC: 0 AN: 66416

Other (OTH) AF: 0.00 AC: 0 AN: 2042

Alfa AF: 0.00 Hom.: 0

Bravo AF: 0.0000113

ClinVar

ClinVar submissions as Germline

Significance: Likely benign

Revision: criteria provided, single submitter

Pathogenic	VUS	Benign	Condition
-	-	1	not provided (1)

Computational scores

Source: dbNSFP v4.9

Name	Calibrated prediction	Score	Prediction
BayesDel_noAF	Benign	-0.39
CADD	Benign	16
DANN	Uncertain	0.97
PhyloP100		2.2
PromoterAI		-0.013	Neutral

Splicing

Name	Calibrated prediction	Score	Prediction
SpliceAI score (max)		0.010		Details are displayed if max score is > 0.2

Find out detailed SpliceAI scores and Pangolin per-transcript scores at spliceailookup.broadinstitute.org

Other links and lift over

dbSNP: rs1254511984; hg19: chr17-48423547;